Muscle SpasticityPhase 1/2NCT00358293
Study of Nighttime Dosing of Sublingual Tizanidine (12 mg) in Multiple Sclerosis (MS) Patients With Significant Spasticity
A Phase 1/2 study testing Tizanidine (sublingual or oral) in people with Muscle Spasticity, run by Teva GTC at 1 site in Israel.
Trial summary
Nightly administration of 8 mg of a unique sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve next-day spasticity, about 12 hours following dosing in 20 multiple sclerosis (MS) patients. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Muscle Spasticity
- What is being tested?
- Tizanidine (sublingual or oral)
- Type of treatment
- Pill or oral medicine
- How many people
- 20 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2006to Feb 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients between the ages of 20-65
- Definitive diagnosis of MS, with Expanded Disability Status Scale (EDSS) less than 6.5 at screening
- Has significant spasticity (total Ashworth => 6) at screening
- Can maintain sleep regimens of at least 5 hours nightly for study duration
- May be allowed to take other anti-spasticity medication during study (including oral baclofen) as per individual dosing regimen, with the following qualifications:
- No dose after 6pm on any study day
- No dose at all on a clinic evaluation day (Visits 3, 4, 5)
- Females must agree to use a medically accepted form of birth control, be surgically sterile, or be two years post-menopausal. Oral contraception is contraindicated with tizanidine use.
Who cannot join
- Acute MS exacerbation requiring treatment with steroids within 30 days of screening
- Initiation of discontinuation of interferon beta within 30 days of screening
- Use of baclofen pump
- Use of CYP1A2 inhibitors during study
- Taking medications that would potentially interfere with the actions of the study medication or outcome variables, including: sedatives, stimulants, anti-hypertensives, tricyclic antidepressants, etc.
- Previous diagnosis of a sleep disorder, distinct from MS, such as obstructive sleep apnea or narcolepsy
Show all 15Show fewer
- Score >18 on Beck Depression Inventory at screening
- Changes in chronic oral medications within 2 weeks of baseline and during study
- Significant abnormalities in screening lab parameters (ex: ALT, AST, bilirubin > 2 x upper limit of normal [ULN]; creatinine > 2 mg/dl; white blood cell [WBC] < 2,300; platelets < 80,000).
- Previous history of dementia, unstable psychiatric disease, or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurological, or cerebral disease
- History of allergy to tizanidine or any inactive component (including lactose intolerance) of test or reference formulation
- History of substance abuse within the past 12 months
- Within 30 days of baseline, worked a rotating or nighttime shift
- Participation in another clinical trial within 30 days of baseline
- Patients who are uncooperative or unwilling to sign consent form
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind, Randomized, Crossover Study to Evaluate the Clinical Efficacy and Safety of Oral Tizanidine HCl (12 mg) Versus Novel Sublingual Tizanidine HCl (12 mg) for the Treatment of Spasticity in MS Patients
Nightly administration of 8 mg of a unique sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve next-day spasticity, about 12 hours following dosing in 20 multiple sclerosis (MS) patients. This improvement was statistically significant when compared to oral tizanidine dosing. The current study is being undertaken to see if increasing the dose to 12 mg once nightly will result in an even greater improvement, with a longer effect, i.e., next day improvement in spasticity both in the morning as well as in the late afternoon.
Read the detailed description
Sublingual tizanidine, a novel test formulation of the known effective antispasticity agent, has been shown to have a unique pharmacokinetic profile [(i.e., nearly twice the bioavailability/AUC), but with little or no increase in peak plasma levels (Cmax) as compared to oral tizanidine (Zanaflex)]. When administered nightly to 20 MS patients, at a dose of 8 mg, it was shown to improve next-day spasticity (statistically significant improvement in Ashworth scores) about 12 hours post-dosing), improvement in nighttime (first quartile) sleep efficiency (as demonstrated by actigraphic measurement), and no increase in daytime somnolence.
Current study is being undertaken to evaluate if increased dosing (12 mg once nightly) of sublingual tizanidine (vs. oral) will show a concomitant increase in clinical effect, i.e., longer improvement, with next-day spasticity score improvement both in AM (as previously) as well as at PM (late afternoon) evaluation, with no increase in daytime somnolence.
- Conditions
- Muscle Spasticity
- Being tested
- Tizanidine (sublingual or oral)
- Keywords
- Multiple Sclerosis, Spasticity, Sublingual Tizanidine, Ashworth Scores, Spasticity in Multiple Sclerosis Patients
- Medical subject headings
- Muscle Spasticity, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tizanidine (sublingual or oral)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy - improvement in next-day spasticity (Ashworth scores)
Safety - no increase in next-day somnolence (measured objectively using PVT psychomotor vigilance task monitoring) and subjectively, using Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires
Secondary outcomes (1)
Secondary clinical efficacy - objective measure of sleep (actigraphy measures)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2006 (estimated)
- Study startDec 2006
- Study completionFeb 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle SpasticityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 20 participants
Sponsor and investigators
- Lead sponsor
- Teva GTC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Arnon Karni, MD, Principal investigator, Department of Neurology, Tel Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00358293
- Sponsor's protocol ID
- Protocol C2/5/TZ-MS-05
- Status last verified
- Apr 2007
- First submitted
- 27 Jul 2006
- Last updated
- 21 Jan 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Crossover Study to Evaluate the Clinical Efficacy and Safety of Oral Tizanidine HCl (12 mg) Versus Novel Sublingual Tizanidine HCl (12 mg) for the Treatment of Spasticity in MS Patients
- ClinicalTrials.gov ID
- NCT00358293
- Acronym / sponsor ID
- Protocol C2/5/TZ-MS-05
- Conditions
- Muscle Spasticity
- Keywords
- Multiple Sclerosis, Spasticity, Sublingual Tizanidine, Ashworth Scores, Spasticity in Multiple Sclerosis Patients
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- Teva GTCIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Study completion
- Feb 2007 (actual)
- First posted
- 31 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nightly administration of 8 mg of a unique sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve next-day spasticity, about 12 hours following dosing in 20 multiple sclerosis (MS) patients. This improvement was statistically significant when compared to oral tizanidine dosing. The current study is being undertaken to see if increasing the dose to 12 mg once nightly will result in an even greater improvement, with a longer effect, i.e., next day improvement in spasticity both in the morning as well as in the late afternoon.
Detailed description
Sublingual tizanidine, a novel test formulation of the known effective antispasticity agent, has been shown to have a unique pharmacokinetic profile [(i.e., nearly twice the bioavailability/AUC), but with little or no increase in peak plasma levels (Cmax) as compared to oral tizanidine (Zanaflex)]. When administered nightly to 20 MS patients, at a dose of 8 mg, it was shown to improve next-day spasticity (statistically significant improvement in Ashworth scores) about 12 hours post-dosing), improvement in nighttime (first quartile) sleep efficiency (as demonstrated by actigraphic measurement), and no increase in daytime somnolence.
Current study is being undertaken to evaluate if increased dosing (12 mg once nightly) of sublingual tizanidine (vs. oral) will show a concomitant increase in clinical effect, i.e., longer improvement, with next-day spasticity score improvement both in AM (as previously) as well as at PM (late afternoon) evaluation, with no increase in daytime somnolence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients between the ages of 20-65
- Definitive diagnosis of MS, with Expanded Disability Status Scale (EDSS) less than 6.5 at screening
- Has significant spasticity (total Ashworth => 6) at screening
- Can maintain sleep regimens of at least 5 hours nightly for study duration
- May be allowed to take other anti-spasticity medication during study (including oral baclofen) as per individual dosing regimen, with the following qualifications:
Key exclusion criteria (15 listed)
- Acute MS exacerbation requiring treatment with steroids within 30 days of screening
- Initiation of discontinuation of interferon beta within 30 days of screening
- Use of baclofen pump
- Use of CYP1A2 inhibitors during study
- Taking medications that would potentially interfere with the actions of the study medication or outcome variables, including: sedatives, stimulants, anti-hypertensives, tricyclic antidepressants, etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tizanidine (sublingual or oral) | Drug | – |
Primary outcome
Clinical efficacy - improvement in next-day spasticity (Ashworth scores)
Safety - no increase in next-day somnolence (measured objectively using PVT psychomotor vigilance task monitoring) and subjectively, using Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires
1 secondary outcome
Secondary clinical efficacy - objective measure of sleep (actigraphy measures)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2009.
Related trials for Muscle Spasticity
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Recruiting
Intrathecal Baclofen and Pediatric Dystonia
Dystonic Cerebral Palsy
RecruitingPhase 4
Individualised Cryoneurolysis to Treat Pain in the Context of Spasticity in the Upper and Lower Extremities
Centreal Neurological Condition, Acquired Brain Injury (Including Stroke)
Not yet recruitingObservational study
Peripheral Neurotomies of the Upper Limb in Children With Cerebral Palsy.
Cerebral Palsy Infantile, Upper Limb Spasticity
Not yet recruitingEarly Phase 1
Early Botulinum Toxin for Muscle Stiffness Reduction in First-Time Stroke Patients: Improving Recovery and Independence
Spasticity, Stroke
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnon Karni, MD principal investigator
Department of Neurology, Tel Aviv Sourasky Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tizanidine (sublingual or oral) in people with Muscle Spasticity, run by Teva GTC at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy - improvement in next-day spasticity (Ashworth scores). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2009.